RNA Hydrogel Self-Assembly via Sequence Motifs
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Solution Overview
Problem
RNA has not been known to form hydrogels due to its single-stranded nature and lack of functional parts for network assembly, unlike DNA which can form hydrogels through base pairing interactions.
Innovation Solution
Identification of specific RNA sequences, such as CZ and 2CZ aptamers, that self-assemble into hydrogels through unique sequence motifs, enabling non-covalent interactions to form a polymeric network structure.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If RNA is used as a single-stranded molecule, then it maintains its natural flexibility and biological function, but it cannot form hydrogels due to lack of network assembly capability
Solution Approach 1:
The RNA molecule is divided into distinct functional domains: a hydrogel-forming domain with specific secondary structure motifs and a cargo-loading domain. This segmentation allows the RNA to simultaneously achieve hydrogel network assembly while maintaining the capacity for therapeutic function, resolving the contradiction between versatility and structural simplicity
Solution Approach 2:
The invention embeds the cargo (small interfering RNA, antisense RNA, or mRNA) within the hydrogel network formed by the scaffold RNA. The cargo is nested within the three-dimensional matrix created by the self-assembling RNA chains, allowing the system to provide both structural function (hydrogel) and therapeutic function (cargo delivery) in a unified structure
2Adaptability or versatility
If DNA is used to form hydrogels through base pairing interactions, then hydrogel formation is achieved, but RNA cannot form hydrogels due to its single-stranded nature
Solution Approach 1:
The invention changes the structural parameters of RNA by introducing specific secondary structures (hairpin loops, bulges, and stem regions) that enable intermolecular base pairing. These parameter changes allow RNA to transition from a flexible single-stranded molecule to a structured network-forming molecule while maintaining RNA-specific properties
Solution Approach 2:
The hydrogel system functions as a composite material where the scaffold RNA provides the structural matrix and the cargo RNA molecules provide the therapeutic function. This composite approach allows the system to achieve both structural stability for hydrogel formation and functional versatility for therapeutic applications
3Ease of manufacture
If specific RNA sequences with unique motifs are introduced, then hydrogel formation through self-assembly is enabled, but the molecular design complexity increases
Solution Approach 1:
The scaffold RNA sequence is designed with intrinsic self-assembly capabilities through embedded secondary structure motifs. The molecule autonomously forms the hydrogel network through its own structural properties without requiring external assembly factors or complex processing, achieving ease of manufacture through self-service
Solution Approach 2:
The scaffold RNA design incorporates universal structural motifs (hairpin loops, stems, and bulges) that can be adapted to different cargo types (siRNA, antisense RNA, mRNA). This universal design approach allows the same basic structural framework to serve multiple therapeutic functions, reducing overall design complexity while maintaining versatility
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The RNA hydrogels exhibit viscoelastic properties, with the ability to form and re-form at specific temperatures, and can be used for applications like drug delivery and tissue engineering, offering a new platform for biomedical applications.
Implementation Method 1
unique sequence motifs, enabling non-covalent interactions to form a polymeric network structure
Implementation Method 2
specific RNA sequences, such as CZ and 2CZ aptamers, that self-assemble into hydrogels
Implementation Method 3
The RNA hydrogels exhibit viscoelastic properties
Implementation Method 4
the ability to form and re-form at specific temperatures
Data Source
AI summary
The disclosure relates to synthetic oligonucleotides that are unique in that they are RNA molecules that have the capacity to form a hydrogel. Also disclosed are DNA oligonucleotides that encode the RNA oligos so that the oligos can be prepared using in vitro transcription. The disclosure further pertains to pharmaceutical compositions comprising these hydrogels.